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Key features of the genetic architecture and evolution of host-microbe interactions revealed by high-resolution genetic mapping of the mucosa-associated gut microbiome in hybrid mice

View ORCID ProfileShauni Doms, View ORCID ProfileHanna Fokt, View ORCID ProfileMalte Christoph Rühlemann, View ORCID ProfileCecilia J. Chung, View ORCID ProfileAxel Künstner, View ORCID ProfileSaleh Ibrahim, View ORCID ProfileAndre Franke, View ORCID ProfileLeslie M. Turner, View ORCID ProfileJohn F. Baines
doi: https://doi.org/10.1101/2021.09.28.462095
Shauni Doms
1Max Planck Institute for Evolutionary Biology, Plön, Germany
2Section of Evolutionary Medicine, Institute for Experimental Medicine, Kiel University, Kiel, Germany
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  • ORCID record for Shauni Doms
Hanna Fokt
1Max Planck Institute for Evolutionary Biology, Plön, Germany
2Section of Evolutionary Medicine, Institute for Experimental Medicine, Kiel University, Kiel, Germany
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Malte Christoph Rühlemann
3Institute for Clinical Molecular Biology (IKMB), Kiel University, Kiel Germany
4Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany
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Cecilia J. Chung
1Max Planck Institute for Evolutionary Biology, Plön, Germany
2Section of Evolutionary Medicine, Institute for Experimental Medicine, Kiel University, Kiel, Germany
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Axel Künstner
5Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany
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Saleh Ibrahim
5Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany
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Andre Franke
3Institute for Clinical Molecular Biology (IKMB), Kiel University, Kiel Germany
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Leslie M. Turner
7Milner Centre for Evolution, Department of Biology & Biochemistry, University of Bath, United Kingdom
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  • For correspondence: l.m.turner@bath.ac.uk baines@evolbio.mpg.de
John F. Baines
1Max Planck Institute for Evolutionary Biology, Plön, Germany
2Section of Evolutionary Medicine, Institute for Experimental Medicine, Kiel University, Kiel, Germany
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  • For correspondence: l.m.turner@bath.ac.uk baines@evolbio.mpg.de
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Abstract

Determining the forces that shape diversity in host-associated bacterial communities is critical to understanding the evolution and maintenance of metaorganisms. To gain deeper understanding of the role of host genetics in shaping gut microbial traits, we employed a powerful genetic mapping approach using inbred lines derived from the hybrid zone of two incipient house mouse species. Further, we uniquely performed our analysis on microbial traits measured at the gut mucosal interface, which is in more direct contact with host cells and the immune system. A high number of mucosa-associated bacterial taxa have significant heritability estimates; heritabilities are greater for 16S rRNA transcript-compared to gene copy-based traits, and interestingly, are positively correlated with cospeciation rate estimates. Genomewide association mapping identifies 443 loci influencing 123 taxa, with narrow genomic intervals pinpointing promising candidate genes and pathways. Importantly, we identified an enrichment of candidate genes associated with several human diseases, including inflammatory bowel disease, and functional categories including innate immunity and G-protein-coupled receptors. These results highlight key features of the genetic architecture of mammalian host-microbe interactions and how they diverge as new species form.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://github.com/sdoms/mapping_scripts

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted November 09, 2021.
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Key features of the genetic architecture and evolution of host-microbe interactions revealed by high-resolution genetic mapping of the mucosa-associated gut microbiome in hybrid mice
Shauni Doms, Hanna Fokt, Malte Christoph Rühlemann, Cecilia J. Chung, Axel Künstner, Saleh Ibrahim, Andre Franke, Leslie M. Turner, John F. Baines
bioRxiv 2021.09.28.462095; doi: https://doi.org/10.1101/2021.09.28.462095
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Key features of the genetic architecture and evolution of host-microbe interactions revealed by high-resolution genetic mapping of the mucosa-associated gut microbiome in hybrid mice
Shauni Doms, Hanna Fokt, Malte Christoph Rühlemann, Cecilia J. Chung, Axel Künstner, Saleh Ibrahim, Andre Franke, Leslie M. Turner, John F. Baines
bioRxiv 2021.09.28.462095; doi: https://doi.org/10.1101/2021.09.28.462095

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